Editorial: Personalizing Treatment in IBD: Hype or Reality in 2020?

[No abstract available

Small and large intestine (II): Inflammatory bowel disease, short bowel syndrome, and malignant tumors of the digestive tract

The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to har-bor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indi-cations for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas). © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Are Steroids Still Useful in Immunosuppressed Patients With Inflammatory Bowel Disease? A Retrospective, Population-Based Study

Background: Effectiveness of corticosteroids in immunosuppressed patients with inflammatory bowel disease (IBD) has not been completely elucidated. Aims: To assess the effectiveness and examine the long-term follow-up of systemic or low-bioavailability oral steroid treatment for moderate flare-ups in patients treated with immunosuppressive drugs. Methods: Immunosuppressed patients with inflammatory bowel disease (IBD) from our population-data registry were analyzed. For statistical analysis, the chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis were used as appropriate. Results: A total of 392 patients with IBD and a median of 82 (range, 6–271) months of immunosuppressive (IMM) treatment were identified. The mean follow-up was 87 months (range, 6–239 months). A total of 89 patients (23%) needed at least one steroid course during their follow-up. Average time from IMM to steroid treatment was 26 (range, 6–207) months. In patients with CD, fibrostenotic (B2) and fistulizing (B3) behaviors [p = 0.005; odds ratio (OR): 2.284] were risk factors for using steroids after IMM treatment. In patients with UC, no statistically significant variables were identified. Of the 89 patients who received one first steroid course, 49 (55%) stepped up to biological treatment or surgery after a median of 13 months (range, 0–178), 19 (21%) were treated with repeated steroid courses, and 31 (35%) required no further treatment. Patients with CD had a higher risk (p = 0.007; OR: 3.529) of receiving biological treatment or surgery than patients with UC. The longer the patients with UC (more months) spent using steroids, the greater the risk of requiring treatment with biological drugs or surgery (p = 0.009). Conclusion: A total of 23% of the immunosuppressed patients with IBD received at least one course of steroid treatment. In patients under immunosuppression treated with at least a course of steroids, CD patients were more likely stepped up to biologics and/or surgery than UC patients. In patients with CD, B2/B3 behavior pattern were significant risk factors. After one course of steroids only 35% of immunosuppressed IBD patients remained in remission without needing treatment scalation. © Copyright © 2021 Sicilia, Arias, Hontoria, García, Badia and Gomollón

La enfermedad inflamatoria intestinal y los riesgos de enfermedad cardiovascular

La enfermedad inflamatoria intestinal (EII), comprende tanto a la colitis ulcerosa como a la enfermedad de Crohn, entidades consideradas enfermedades inmunomediadas, sistémicas y de curso crónico que conllevan a menudo el desarrollo de manifestaciones extraintestinales. A pesar de que el estudio de las comorbilidades haya sido desarrollado tradicionalmente en contexto de otras enfermedades inflamatorias sistémicas, este concepto está emergiendo también en la EII. Multitud de patologías han sido vinculadas a la EII, entre las que destaca la enfermedad cardiovascular, la primera causa de muerte en los países desarrollados. Los pacientes con EII están expuestos a un mayor riesgo de entidades tales como arterosclerosis precoz e infarto de miocardio, o trombosis venosas y tromboembolismo pulmonar. El objetivo de esta revisión es hacer una aproximación a la fisiopatología de las diferentes manifestaciones de la enfermedad cardiovascular en los pacientes con EII y de cómo prevenirlas. Inflammatory bowel disease (IBD) includes both ulcerative colitis and Crohn's disease, which are well recognised as chronic systemic and immune-mediated conditions that frequently involve extraintestinal manifestations. Although comorbidities have long been the subject of research in other chronic inflammatory diseases, this concept is also emerging in IBD. Many pathologies have been linked to IBD, including cardiovascular disease, which is the main cause of death in developed countries. IBD patients are at increased risk of conditions such as early atherosclerosis and myocardial infarction or venous thrombosis and pulmonary thromboembolism. The aim of this review is to make an approximation of the physiopathology of the different manifestations of cardiovascular disease in patients with IBD and how to prevent them

Oral cyanocobalamin is effective in the treatment of vitamin B12 deficiency in crohn’s disease

Cobalamin deficiency is common in patients with Crohn’s disease (CD). Intramuscular cobalamin continues to be the standard therapy for the deficiency and maintenance treatment in these patients, although oral route has been demonstrated to be effective in other pathologies with impaired absorption. Our aims were to evaluate the efficacy of oral therapy in the treatment of cobalamin deficiency and in long-term maintenance in patients with Crohn’s disease. We performed a multicenter retrospective cohort study that included 94 patients with Crohn’s disease and cobalamin deficiency. Seventy-six patients had B12 deficiency and 94.7% of them normalized their cobalamin levels with oral treatment. The most used dose was 1 mg/day, but there were no significant differences in treatment effectiveness depending on the dose used (=1 mg/24 h vs. <1 mg/24 h). Eighty-two patients had previous documented B12 deficiency and were treated with oral B12 to maintain their correct cobalamin levels. After a mean follow-up of 3 years, the oral route was effective as maintenance treatment in 81.7% of patients. A lack of treatment adherence was admitted by 46.6% of patients in who the oral route failed. In conclusion, our study shows that oral cyanocobalamin provides effective acute and maintenance treatment for vitamin B12 deficiency caused by CD with or without ileum resection

Disease severity in familial cases of IBD

Background: Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. Aim: To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. Methods: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. Results: In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25–44] vs 37 years [IQR 27–49]; p b 0.0001); (CD: 27 years [IQR 21–35] vs 29 years [IQR 22–40]; p b 0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p = 0.04); (CD: 30.1% vs 23.6%; p b 0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p = 0.0001), penetrating behavior (21% vs 17.6%; p = 0.01) and perianal disease (32% vs 27.1%; p = 0.003). Differences are not influenced by degree of consanguinity. Conclusion: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients with Inflammatory Bowel Disease: Results from the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn''s disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

Systemic Inflammation in Preclinical Ulcerative Colitis

Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-¿B, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors. © 2021 The Author

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland